The Biesecker Pediatric Liver Center at The Children’s Hospital of Philadelphia is actively involved in research studies on liver transplantation and immunology.
Transplantation provides a potential cure for end-stage disease affecting various organs and tissues, including end-stage liver disease.
However, while the results of organ transplantation are commonly life-saving, resulting in a return to a normal or near-normal lifestyle and development, this typically entails long-term maintenance immunosuppression. Recognizing that any maintenance drug therapy, especially involving powerful agents like those used for immunosuppression, carries certain risks, our research is focused on understanding the mechanisms of induction and persistence of transplant tolerance, so ultimately transplant recipients will require little or no ongoing drug therapy.
The researchers involved in the transplantation and immunobiology group undertake multifaceted investigations into the mechanisms of graft rejection and tolerance induction, using clinical samples and various experimental transplant models. The strength of this research lies in the use of in vivo models in which specific genes of interest are either deleted or over-expressed to determine their importance in the overall regulation of host responses post-transplant.
Ongoing studies involve the:
- Role of chemokine-dependent pathways in graft rejection and tolerance;
- Identification and characterization of co-stimulatory pathways;
- Manipulation of the NFkB pathway; and
- Development of practical tools to enhance the function of regulatory T cells to improve outcomes post-transplant.
Additional research initiatives of this group focus on the molecular and immunologic approaches to dissect fundamental steps in T-cell regulation, activation and function, in the hopes of identifying new targets for immunoregulation.
Ongoing studies involve cell-cycle regulation, novel transcription factors and regulation of key genes involved in T-cell energy and tolerance, including Foxp3 and its various homologs; and human immune monitoring pre- and post-transplant.